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    Why the ApoB cholesterol test is a better predictor than standard tests

    It’s a familiar ritual, the regular cholesterol test. You wake up and skip breakfast – not even coffee – and sit blearily in the exam room, looking at the ceiling as the phlebotomist slides a needle into your vein. A few days later, the results show up in your chart.

    For decades, primary physicians and cardiologists have focused on two numbers: LDL or low-density lipoproteins, known as “bad cholesterol,” and HDL or high-density lipoproteins, a.k.a. “good cholesterol.” The two numbers are considered key determinants of a patient’s cardiovascular disease risk.

    But a growing number of physicians and researchers are saying that it’s time to move beyond this timeworn emphasis on “good” or “bad” cholesterol.

    Instead, there’s a potentially more accurate marker of heart attack risk: apolipoprotein B (“apoB” for short).

    A better cholesterol test

    Research shows that heart risk is driven by the number and type of cholesterol particles in the blood — and not so much by the cholesterol itself. ApoB is the particle that actually carries the cholesterol in the circulation.

    Decades’ worth of evidence show that measuring the number of apoB particles in the blood predicts cardiovascular risk far more accurately than the standard good-cholesterol/bad-cholesterol lipid panel, but cholesterol guidelines barely acknowledge its existence. Current guidelines only offer it as an option for certain high-risk patients.

    As a result, most patients and even many doctors have no idea that a better cholesterol test even exists. “Old habits die hard,” says Ann Marie Navar, a preventive cardiologist at UT Southwestern Medical Center in Dallas.

    The standard cholesterol panel calculates the total quantity or concentration of “bad” cholesterol or LDL in the blood, in milligrams per deciliter (technically, LDL-C). Because cholesterol is a fatty substance and thus not water-soluble, it must be carried around in little particles known as lipoproteins.

    Testing for apoB, a protein on the outside of LDL-carrying particles, counts the number of these lipoprotein particles in the blood. In addition to LDL, it also captures other types of cholesterol such as IDL (intermediate-density lipoproteins) and VLDL (very low-density lipoproteins), which carry triglycerides.

    Why is this important? As our understanding of heart disease improves, scientists are recognizing that apoB particles are more likely to become lodged in the arterial wall and cause it to thicken and eventually form atherosclerotic plaques. Thus, the total number of apoB particles matters more than the overall quantity of cholesterol that they carry.

    In a majority of people, apoB and LDL-C track fairly closely, says Allan Sniderman, a professor of cardiology at McGill University in Montreal. But some people have a “normal” amount of LDL-C, but a high concentration of apoB particles – a condition called “discordance,” which means they are at greater risk. But conventional cholesterol panels don’t catch those patients.

    “Two people can have the exact same amount of cholesterol and a vastly different number of particles bouncing around against the arterial wall,” says Sniderman, who has been researching apoB for decades.

    Why people with low cholesterol still have heart attacks

    Discordance may help explain why people with optimal cholesterol numbers still have heart attacks. A widely-cited 2009 study found that more than half of patients admitted to a hospital following a heart attack or other cardiovascular event had “normal” levels of LDL cholesterol, using standard measurement techniques.

    Testing for apoB rather than LDL-C could identify people who are at high risk due to this discordance. “We’re losing people that we could be saving,” says Sniderman.

    There is no shortage of evidence in favor of apoB versus traditional LDL-C testing. In the last several years, three large clinical trials (called IMPROVE-IT, FOURIER, and ODYSSEY) found strongly in favor of apoB as a better risk predictor than LDL-C.

    “There already was quite a lot of data for apoB,” says Seth Martin, a professor of medicine and director of the Advanced Lipid Disorders Program at Johns Hopkins University. “But guideline recommendations around apoB don’t give a lot of guidance.” Martin is part of a group of cholesterol experts working with the National Lipid Association to help doctors implement and understand apoB testing.

    As it stands, U.S. cholesterol guidelines do not suggest that doctors test for apoB in all patients, just those with certain risks, such as those high triglycerides. As a result, some insurers will refuse to pay for the test (I got charged $25 by United Healthcare earlier this year). But some international lipid guidelines support apoB testing.

    Salim Virani, a co-author of the latest U.S. cholesterol guidelines, issued in 2018, acknowledges that apoB is “a superior predictor of cardiovascular events when compared with LDL cholesterol.” But he says that another number on the standard lipid panel effectively conveys the same information: non-HDL cholesterol (total cholesterol minus HDL cholesterol).

    “Although clinicians could measure ApoB if needed, non-HDL cholesterol offers free information from a standard lipid panel that clinicians could use for risk stratification above and beyond LDL cholesterol,” says Virani, a former professor at Baylor University medical school who is now vice provost for research at Aga Khan University in Karachi, Pakistan.

    Proponents of apoB say it offers more specificity than non-HDL cholesterol — and helps doctors identify individuals who might otherwise slip through the cracks with “normal” cholesterol numbers. “It’s not that non-HDL or LDL-C are bad lipid markers – it’s that apoB is better,” says John Wilkins, a professor at Northwestern University’s Feinberg School of Medicine. “It’s easy enough to add to a standard lipid panel.”

    ApoB testing may be especially important in people younger than 40, Wilkins adds. He co-authored a 2016 study showing that younger people with high apoB levels but normal LDL were at greater risk for coronary artery calcification, a relatively advanced stage of heart disease. “There’s a very clear correlation between apoB levels and disease later in life,” he says.

    Patients who discover they have high apoB levels likely will be advised to adopt the same treatments and lifestyle changes used for other indicators of high cholesterol, including daily exercise, a diet with more plant-based foods and less saturated fat and a cholesterol-lowering statin or other lipid-lowering drug therapies.

    “The challenge is that atherosclerosis progresses silently for years or decades,” says Martin, of Johns Hopkins. “If someone is developing plaque, due to high lipids or other factors, it could be a completely silent process — until a plaque breaks and they have a heart attack. So it’s important even at an earlier age to have this on your radar, especially if you have a particular family history of early disease,” he says. “It’s about getting ahead of the curve.”

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